Impaired endocrine and exocrine pancreatic functions in copper-deficient rats: the effect of gender

OBJECTIVE: To examine the effect of gender on endocrine and exocrine pancreatic function in female and male rats fed from weaning a copper-deficient diet. METHODS: Weanling male and female rats were fed a copper-deficient or adequate diet for 4 weeks. Rats were sacrificed after an overnight fast. Livers and pancreata were removed, weighed and the concentrations of copper and iron were determined. In addition, insulin was measured in pancreatic tissue and plasma. Lipase and amylase activities were measured in pancreas. Lipid peroxidation was assessed in liver. RESULTS: Copper deficiency in the male resulted in a profound reduced glandular mass of the pancreas. The pancreas continued low activities of lipase and amylase but excessive levels of insulin. Iron retention in the pancreas of the copper-deficient male rat was greater than in the female counterpart. Effects of copper deficiency in female rats on pancreas mass and endocrine pancreas were of lesser magnitude compared with males. Plasma insulin in the female rat was much higher than in the male rat. Hepatic lipid peroxidation was increased by copper deficiency in the male rat but was unaffected in the female. CONCLUSIONS: Data show that pancreatic atrophy is more pronounced in males compared with females, and the endocrine pancreas of the male is more susceptible to dietary copper deprivation than the female rat. The greater degree of pancreatic atrophy and associated abnormalities in males compared with females may be related to the greater retention of pancreatic iron and subsequent peroxidative damage.     

Pharmacologic atrial natriuretic peptide reduces human leg capillary filtration

Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethysmography of supine healthy male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n = 6) and during placebo infusion (n = 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma [ANP] from 30 +/- 4 to 2,568 +/- 595 pmol/l. Systemic hemoconcentration occurred during ANP infusion: mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3%, respectively, relative to preinfusion baseline values (p < 0.05). Mean calf filtration, however, was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20% with ANP infusion, whereas blood pressure was unchanged. Calf conductance (blood flow/arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, pharmacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchnic sites or both, while having the opposite effect in the leg.     

Recombinant human growth-regulated oncogene-alpha induces T lymphocyte chemotaxis. A process regulated via IL-8 receptors by IFN-gamma, TNF-alpha, IL-4, IL-10, and IL-13

The human cytokine growth-regulated oncogene (GRO)-alpha is a small glycoprotein secreted by monocytes, endothelial cells, glycoprotein secreted by monocytes, endothelial cells, fibroblasts, synovial cells, and some tumor cells such as melanoma cells. It is structurally related to IL-8 and can activate neutrophils, whereas it induces chemotaxis, exocytosis, and a respiratory burst in neutrophils. To date, its functions on T lymphocytes have not been well established. We report here that recombinant human (rh)GRO-alpha is a potent chemoattractant for freshly isolated T lymphocytes, but not for anti-CD3 mAb-activated T lymphocytes. It attracts CD4+ and CD8+ T lymphocyte subsets to an equal extent. The migrating T lymphocytes toward rhGRO-alpha are predominantly CD45RO+ memory CD4+ and CD8+ subsets. The chemotactic migration of T lymphocytes toward rhGRO-alpha is stimulated via the IL-8 receptors on the cells. This process can be augmented by IFN-gamma and TNF-alpha, and inhibited by IL-4, IL-10, and IL-13. In addition, we also document that on T lymphocytes there exist IL-8 receptors that can be up-regulated by IFN-gamma, TNF-alpha, and IL-2. Our results demonstrate that rhGRO-alpha gene encodes for an inflammatory mediator that stimulates the directional migration of T lymphocytes. It may thus be another important mediator in the diseases in which T lymphocytes form the major constituent of the cellular infiltration.     

Formation of unilamellar liposomes from total polar lipid extracts of methanogens

Unilamellar liposomes were formed by controlled detergent dialysis of mixed micelles consisting of acetone-insoluble total polar lipids extracted from various methanogens and the detergent n-octyl-beta-D-glucopyranoside. The final liposome populations were studied by dynamic light scattering and electron microscopy. Unilamellar liposomes with mean diameters smaller than 100 nm were obtained with lipid extracts of Methanococcus voltae, Methanosarcina mazei, Methanosaeta concilii, and Methanococcus jannaschii (grown at 50 degrees C), whereas larger (greater than 100-nm) unilamellar liposomes were obtained with lipid extracts of M. jannaschii grown at 65 degrees C. These liposomes were shown to be closed intact vesicles capable of retaining entrapped [14C]sucrose for extended periods of time. With the exception of Methanospirillum hungatei liposomes, all size distributions of the different liposome populations were fairly homogeneous.     

Novel systemically active antagonists of the glycine site of the N-methyl-D-aspartate receptor: electrophysiological, biochemical and behavioral characterization

A series of novel tricyclic pyrido-phthalazine-dione derivatives was tested for antagonistic effects at the strychnine-insensitive modulatory site of the N-methyl-D-aspartate (NMDA) receptor (glycineB). All compounds displaced [3H]MDL-105,519 binding to rat cortical membranes with IC50 values of between 90 nM and 3.6 microM. In patch-clamp experiments, steady-state inward current responses of cultured hippocampal neurons to NMDA (200 microM, glycine 1 microM) were antagonized by these same compounds with IC50 values of 0.14 to 13.8 microM. The antagonism observed was typical for glycineB antagonists, i.e., they induced desensitization and their effects were not use or voltage dependent. Moreover, increasing concentrations of glycine were able to decrease their apparent potency. Much higher concentrations (>100 microM) were required to antagonize alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced currents. They were potent, systemically active NMDA receptor antagonists in vivo against responses of single neurons in the rat spinal cord to microelectrophoretic application of NMDA with ID50 values in the low milligram per kilogram i.v. range. They also inhibited pentylenetetrazol-, NMDA- and maximal electroshock-induced convulsions in mice with ED50 values ranging from 8 to 100 mg/kg i.p. The duration of anticonvulsive action was rather short but was prolonged by the organic acid transport inhibitor probenecid (200 mg/kg). The agents tested represent a novel class of systemically active glycineB antagonists with greatly improved bioavailability.     

Perceived family criticism and primary care utilization: psychosocial and biomedical pathways

We explored the relationship of perceived family criticism to subsequent healthcare utilization in patients attending a family medicine center. We examined: a) the relationship of perceived criticism to subsequent utilization for biomedical and psychosocial/somatic problems; b) the mediating effects of self-rated mental health and physical function; and c) the mediating effects of social support. The analyses were adjusted for age, sex, race, education, health insurance, and martial status. Higher perceived criticism predicted more psychosocial/somatic and biomedical visits. The relationship of perceived criticism with psychosocial/somatic visits was entirely mediated through self-rated mental health. The relationship of perceived criticism with biomedical visits was partly mediated through self-rated physical function and, in part, independent. Social support played no role in explaining these relationships. Further research is needed to determine whether lowering perceived family criticism lowers primary care utilization.     

Assessment of nutritional status in CAPD patients: serum albumin is not a useful measure

INTRODUCTION: In CAPD patients serum albumin is frequently used as an index of nutritional status, although it is recognized that hypoalbuminaemia may be caused by many factors. We have further examined the relationship between serum albumin and nutrition. METHODS: Nutritional status was assessed by biochemistry, anthropometry, mid-arm muscle circumference, muscle strength (hand grip and back), and lean body mass (from anthropometry, creatinine kinetics and bioimpedance) in a group of 76 stable CAPD patients. Correlations between biochemical and nutritional parameters were sought and data were compared between patient groups defined by serum albumin (> or = 37 vs < 37 g/l on two occasions 2 months apart) and separately according to subjective global assessment score (normal nutrition, A vs mild to moderate, B, and severe, C, malnutrition). RESULTS: In patients with a low SGA score, actual body weight, body mass index, mid-arm muscle circumference, lean body mass, subscapular skinfold thickness, hand grip strength (males and females) and iliac and triceps skinfold thicknesses and back strength (females only) were all significantly less than in patients with a normal SGA score. In contrast, none of these variables differed in either gender when patients were compared according to serum albumin. Serum albumin was correlated with serum creatinine (r = 0.45, P = 0.01), daily urine protein excretion (r = -0.42, P = 0.02) and uncorrected weekly creatinine clearance (r = -0.39) in females, but not with any index of body composition in either gender. CONCLUSION: Whilst SGA identified a patient group with significantly abnormal body mass, muscle mass and muscle strength, serum albumin did not. Serum albumin is not a useful marker of malnutrition in stable patients on CAPD.